Interleukin-12 enhances contact hypersensitivity by modulating the in vivo cytokine pattern in mice.
It has been proven that interleukin-12 (IL-12) can modify Th1 and Th2 cell-mediated immune diseases by altering the development and cytokine production of the cells. In this study, we investigated the in vivo immunomodulatory effect of recombinant murine IL-12 on contact hypersensitivity, a Th1 cell-mediated disease. For this purpose, Balb/C mice were sensitized with 3% 4-ethyoxymethylene-2-phenyl-oxazol-5-one (OXAZ), and recombinant mouse IL-12 was given simultaneously during the induction phase. Contact allergy was then elicited by ear challenge with 1% OXAZ. We examined the mouse ear swelling response, in vivo cytokine gene expression in the skin and local lymph nodes, and in vitro cytokine production by the spleen lymphocytes. It was found that in vivo IL-12 treatment during the induction phase significantly enhanced the ear swelling response to OXAZ in sensitized mice. Moreover, remarkable mononuclear cell infiltration and edema and higher expression of Th1 cytokine mRNAs (IL-2 and interferon-gamma) in the skin lesion and local lymph nodes were observed in contact allergic mice with IL-12 treatment compared with contact allergic mice without IL-12 treatment. The expression of Th2 cytokine mRNA (IL-4) in the skin lesion and local lymph nodes, however, was largely downregulated, with no change in IL-5 mRNA in IL-12-treated contact allergic mice. We found, unexpectedly, that, similar to the effects on phytohemagglutinin (PHA) stimulated in vitro IL-2 and IFN-gamma production, PHA-induced in vitro IL-4 production was enhanced in the spleen lymphocytes from IL-12-treated contact allergic mice. Our results indicate that exogenous IL-12 enhanced contact hypersensitivity probably because of the in vivo promoting and suppressing effects of IL-12 on Th1 and Th2 gene expression, respectively.
Xu
B
B
Department of Environmental Medicine, Faculty of Medicine, Kagoshima University, Japan.
Aoyama
K
K
Kitani
A
A
Yu
S
S
Matsuyama
T
T
Matsushita
T
T
D000818:Animals; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000187:drug effects* / Q000235:genetics; D003877:Dermatitis, Contact / Q000209:etiology* / Q000473:pathology; D005260:Female; D018664:Interleukin-12 / Q000009:adverse effects* / Q000627:therapeutic use; D008198:Lymph Nodes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000378:metabolism; D018418:Th2 Cells / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D012333:RNA, Messenger; D011994:Recombinant Proteins; D018664:Interleukin-12